tenofovir disoproxil fumarate
Viread

Pharmacologic classification: nucleotide reverse transcriptase inhibitor
Therapeutic classification: antiviral, antiretroviral
Pregnancy risk category B


Available forms
Available by prescription only
Tablets: 300 mg as the fumarate salt (equivalent to 245 mg of tenofovir disoproxil)

Indications and dosages
 HIV-1 infection, with other antiretrovirals. Adults: 300 mg P.O. once daily with a meal. When given with didanosine, give 2 hours before or 1 hour after didanosine.

Pharmacodynamics
Antiviral action: Tenofovir disoproxil fumarate is a prodrug that is hydrolyzed to produce tenofovir. Tenofovir, a nucleoside analogue of adenosine monophosphate, undergoes sequential phosphorylations to yield tenofovir diphosphate. Tenofovir diphosphate is a competitive antagonist of HIV reverse transcriptase, via competition with the natural substrate and through DNA chain termination. These effects result in inhibition of HIV replication.

Pharmacokinetics
Absorption: In fasting patients, tenofovir is poorly absorbed (bioavailability 25%), with peak serum levels occurring in about 1 hour. A high-fat meal delays the peak by 1 hour but increases bioavailability to 40%.
Distribution: Tenofovir has low binding to plasma (0.7%) and serum proteins (7.2%).
Metabolism: Neither tenofovir nor tenofovir disoproxil fumarate is metabolized by liver enzymes, including the CYP450 enzymes.
Excretion: Renal, through glomerular filtration and active tubular secretion.

Route Onset Peak Duration
P.O. Unknown 1-2 hr Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drugs or its components. Don’t use in patients with renal insufficiency (creatinine clearance less than 60 ml/minute). Use very cautiously in patients with risk factors for liver disease or with hepatic impairment.

Interactions
Drug-drug. Didanosine (buffered formulation): Increases didanosine bioavailability. Monitor patient for didanosine-related adverse effects, such as bone marrow suppression, GI distress, and peripheral neuropathy. Give tenofovir 2 hours before or 1 hour after didanosine.
Drugs that reduce renal function or compete for renal tubular secretion (acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir): Increases levels of tenofovir or other renally eliminated drugs. Monitor patient for adverse effects.

Adverse reactions
CNS: asthenia, headache.
GI: abdominal pain, anorexia, diarrhea, flatulence, nausea, vomiting.
GU: glycosuria.
Hematologic: neutropenia.
Metabolic: hyperglycemia.

Effects on lab test results
• May increase amylase, AST, ALT, CK, serum glucose, urine glucose, and triglyceride levels.
• May decrease neutrophil count.

Overdose and treatment
Dosages as high as 600 mg/day have caused no serious adverse effects. The effects of hemodialysis or peritoneal dialysis on tenofovir aren’t known.
 Monitor patient for adverse events and begin standard supportive treatment if they occur.

Special considerations
• Antiretrovirals, alone or combined, have been linked to lactic acidosis and severe (including fatal) hepatomegaly with steatosis. These effects may occur without elevated transaminase levels. Risk factors include prolonged exposure to antiretrovirals, obesity, and being female. Monitor all patients for hepatotoxicity, including lactic acidosis and hepatomegaly with steatosis.
• Antiretrovirals have been linked to the accumulation and redistribution of body fat, resulting in central obesity, peripheral wasting, and development of a buffalo hump. The long-term effects of these changes are unknown. Monitor patients for changes in body fat.
• Tenofovir may be linked to bone abnormalities (osteomalacia and decreased bone mineral density) and renal toxicity (increased creatinine and phosphaturia levels). Monitor patient carefully during long-term treatment.
• Drug may lead to decreased HIV-1 RNA levels and CD4 cell counts.
• The effects of tenofovir on the progression of HIV infection are unknown.
Pregnant patients
• Because the effects of tenofovir on pregnant women aren’t known, give this drug to pregnant women only if its benefits clearly outweigh the risks.
Breast-feeding patients
• It isn’t known whether tenofovir appears in breast milk. However, women receiving tenofovir for HIV
Breast-feeding patients
• It isn’t known whether tenofovir appears in breast milk. However, women receiving tenofovir for HIV infection shouldn’t breast-feed.
Pediatric patients
• Safety and efficacy haven’t been studied in children.
Geriatric patients
• Use tenofovir cautiously in geriatric patients because these patients are more likely to have renal impairment and concurrent drug therapy.

Patient education
• Instruct patient to take tenofovir with a meal to enhance bioavailability.
• If patient takes tenofovir and didanosine (buffered form), instruct him to take tenofovir 2 hours before or 1 hour after didanosine.
• Tell patient to report adverse effects, including nausea, vomiting, diarrhea, flatulence, and headache.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use